Osteoporosis is an increasingly important public health concern for women, contributing to over 1.3 million fractures per year. With the increase in the elderly population, a three fold increase in hip fractures, the most costly fracture, has been projected, with costs for treating all osteoporotic fractures increasing from $13.8 Billion in 1995 to $60 Billion by the year 2020. While the effects of dietary and hormonal interventions on BMD are being investigated in the Women's Health Initiative, the effects of exercise, a potentially effective stimulus for slowing and possibly reversing bone loss is not assessed. In this renewal we propose to complete intervention and assessments for a large partially randomized clinical trial evaluating the effect of one year of exercise on total body and regional BMD in two population (hormone replacement therapy (HRT) versus no HRT) of postmenopausal women. We also propose to add measurements of bone biomarkers and endocrine factors to our existing data base to investigate correlates of BMD underlying the potential response to exercise and to extend follow-up for an additional two years to assess the long-term effects in women who continue exercising versus women who do not exercise. We hypothesize that exercise will significantly increase BMD and that exercise plus HRT is a more effective stimulus than exercise or HRT alone. Thus, exercise will be an efficacious alternative to risk reduction of osteoporosis. The study is unique in its design (random assignment) population (HRT versus no HRT), sample size (N=279), and the comprehensive assessment of physiological, nutritional, and morphological correlates of BMD. Duplicate (one week apart) blood collections and DXA scans are done at each measurement period (baseline 6 and 12 months) to improve precision to follow changes in biomarkers, hormones, soft tissue composition, and axial and appendicular BMD. Extensive dietary intake data are collected using diet records and food frequency questionnaires. The exercise program (progressive resistance exercise and weight bearing aerobic exercise) is designed to provide high strain magnitudes, rates and a diverse distribution, all thought to be osteogenic stimuli. Exercise compliance is carefully monitored through extensive workout records of exercise frequency, intensity duration and type, and by measuring muscle strength gains. Study adherence for the initial four cohorts (of 6 cohorts) was 92 percent. Thus, as we show, we have excellent power to assess short-term and long- term exercise effects. Because of the paucity of information regarding long term effects of exercise, and because of the increased emphasis called for in the scientific community for evaluating the long-term efficacy of exercise for osteoporosis prevention, this comprehensive one year clinical trial and two year follow-up will make an important contribution to a valid prescription of exercise for the prevention of osteoporosis in two populations (HRT vs no HRT) of postmenopausal women.